The present invention relates to endovascular stents and more particularly pertains to coatings that are applied to stents in order to reduce thrombogenicity.
Stents are implanted within blood vessels in an effort to maintain their patency by preventing collapse of the lumen and/or by impeding restenosis. Unfortunately, the presence of a foreign object within the blood flow may have a thrombogenic effect. It has therefore been found to be desirable to use various anti-coagulant drugs in an effort to reduce the likelihood of the development of restenosis and provide an antithrombogenic effect.
A drug that has been found to be particularly effective for such purpose is heparin. By maintaining an effective concentration of the drug in and about the implantation site until the stent is encapsulated by tissue, the risk of thrombogenesis is substantially mitigated. To that end, various approaches have been employed in the administration of heparin.
While the systemic administration of heparin can cause the implantation site to be subjected to an effective level of heparin, such level of heparin would necessarily also be present throughout the rest of the body which can lead to undesirable side effects such as bleeding. It has therefore been recognized that a regimen wherein the heparin is substantially constrained to the implantation site is far more desirable. An approach that has been devised to achieve such end requires the coating or impregnation of the stent itself with heparin. The heparin is thereby concentrated where it is most needed while its presence, and consequently its effect, throughout the rest of the body is minimized.
Disadvantages associated with heretofore known heparinized stents include, the limited shelf life of such devices, the fact the heparin is degraded when the stent is sterilized either by heat or by exposure to ethylene dioxide, the inability of the physician to alter the dosage that the patient is subjected to and the inability to replenish any heparin that may be lost while the device is deployed. Additionally, the cost of heretofore known heparinized stent devices has been very high as it necessarily includes the costs associated with the stringent regulatory requirements attendant a drug containing device.
The prior art has been unable to overcome these disadvantages and shortcomings and a new approach is needed to safely, effectively, and economically deliver heparin to an implantation site.
The present invention provides for the coating of an implantable endovascular device to facilitate the subsequent loading of heparin onto its surface. Such loading can be achieved in vitro just prior to implantation or preferably, in vivo after the device is in place. As a result, the device has a considerably longer shelf-life than heparin-containing devices, the need for special handling and sterilization procedures associated with heparin-containing devices is obviated, and the dosage of heparin can be readily tailored to an individual patient""s needs including any adjustment that may be required after the device has been deployed. An additional advantage provided by such a device is that it is not subject to the stringent regulatory requirements associated with drug-containing devices.
More particularly, the present invention provides for the coating of stent surfaces with a material or combination of materials that are selected for their ability to adhere to the stent surface, to attract heparin and to form preferably an ionic bond therewith. The heparin is attracted by and attaches to functional groups incorporated in the coating which may include primary, secondary, and/or tertiary amines or other functionalities such as carboxyl groups.
The heparin-attracting coating may be applied so as to encapsulate the entire stent or alternatively, to cover only selected surfaces thereof. By limiting coverage to only the inner surface of the stent, i.e., the surface that is directly exposed to blood flow, a much higher level of heparin can be loaded onto the stent than would be safe if such level were in direct contact with the vessel wall. A toxic effect on the vessel wall is thereby avoided while the blood is exposed to a more effective concentration of heparin. Alternatively, it may be deemed sufficient to coat only the ends of the stent, i.e., where disturbance of flow is greatest and where thromboses are most likely to occur.
The coating may be applied by different processes such as by dipping, spraying or molding. The preferred method is by plasma deposition wherein a base layer, selected for its ability to adhere to the stent surface, is first deposited on the stent followed by the deposition of a top layer thereon that is selected for its ability to bond to the base layer and to avail the appropriate functional groups for bonding to the heparin.